a study of donafenib plus s-1 in treating patients with metastatic pancreatic cancer after chemotherapy with nab-paclitaxel plus gemcitabine regimen

Conditions: Metastatic Pancreatic Cancer

Summary: this is a single arm, open label phase ii clinical trial to evaluate the efficacy and safety of donafenib combined with s-1 in treating patients with metastatic pancreatic cancer after chemotherapy with nab-paclitaxel plus gemcitabine regimen.

while ng ( nab-paclitaxel + gemcitabine) is one of the preferred first-line chemotherapy for metastatic pancreatic cancer, we have to investigate possible therapeutic options after ng regimen. in this single arm, open-label clinical trial, metastatic pancreatic cancer patients will be received donafenib and s-1. treatment repeats every 3 weeks until the disease recurrence or unacceptable toxicity, death or begin a novel therapeutic. the efficacy and safety data will be assessed through os, orr, dcr, pfs,ttp and adverse effects as graded by nci ctc-ae 5.0.

Eligibility criteria:
inclusion criteria: * informed consent and willing to complete the study according to the protocol. * age ≥ 18 years and ≤ 75 years, and there is no limit on the gender * ecog performance scale 0-1; * diagnosed as pancreatic adenocarcinoma by histology and cytology; * treatment of patients with advanced metastatic pancreatic cancer who have failed with ng (nab-paclitaxel + gemcitabine) regimen(the disease progresses during the course of treatment or within 6 months after the end of treatment, with clear imaging evidence; this does not include patients with intolerable toxicity)； * baseline blood routine and biochemical indexes meet the following criteria: 1. blood routine examination criteria must be met: (no blood transfusion within 14 days) 1. hb≥90g/l； 2. anc≥1.5×109/l； 3. plt≥100×109/l. 2. biochemical tests are subject to the following criteria: 1. bil \<1.25xuln ； 2. alt and ast\<2.5uln； 3. serum creatinine. less than 1.5 times the upper limit of normal value, endogenous creatinine clearance\>60ml/min ( cockcroft-gault formula). 4. albumin≥28g/l. 3. blood coagulation indexes are subject to the following criteria: 1. prothrombin time (pt) and international normalized ratio (inr) ≤1.5 × uln; 2. activated partial thromboplastin time（aptt）≤1.5 × uln. * according to the standard of recist 1.1, there is at least one imaging measurable lesion; * life expectancy ≥ 3 months; * patients and their families were willing to cooperate with follow-up. exclusion criteria: * diagnosis of malignant diseases other than pancreatic cancer within 5 years prior to first administration (excluding cured skin basal cell carcinoma, squamous carcinoma of the skin, and/or resected carcinoma in situ); * medical conditions that affect absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.); * patients with brain metastases or pial metastases; * patients with a clear past history of neurological or psychiatric disorders, including epilepsy or dementia; * comorbidities (e.g., severe or uncontrolled hypertension, severe diabetes, and/or thyroid disease) that, in the investigator's judgment, seriously endanger patients' safety or prevent them from completing the study; * the patient was currently participating in an interventional clinical study or had been treated with another study drug or study device in the 4 weeks prior to initial dosing; * the patient had a history of organ transplantation; * concurrent administration of drugs that may prolong qtc and/or induce tdp; * patients also take drugs that affect drug metabolism; * hiv infection or acute or chronic viral hepatitis (hbsag positive, hbv-dna load ≥500iu/ml and/or hcv antibody positive); * excluded patients with serious cardiovascular disease, including grade ≥ii cardiac dysfunction (nyha criteria); * patients with severe gastrointestinal dysfunction (bleeding, infection, obstruction, or diarrhea greater than grade 1) were excluded; * patients with abnormal coagulation function, bleeding tendency, or receiving thrombolytic or anticoagulant therapy were excluded; * patients with a severe arterial thromboembolism event within 6 months were excluded; * excluding women who are pregnant or breast-feeding.